Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.

Effect of Gualou Xiebai Banxia decoction combined with Danshen Decoction on clinical efficacy of unstable angina with phlegm and blood stasis syndrome

Objective:To observe the clinical efficacy and safety of Gualou Xiebai Banxia decoction combined with Danshen decoction on unstable angina(UA)with phlegm and blood stasis syndrome.Method:Eighty patients with UA were randomly divided into treatment group(40 cases)and control group(40 cases)by random number table.The control group was given conventional western medicine treatment,and the experimental group was given Gualou Xiebai Banxia decoction and Danshen decoction on the basis of the control group.Both groups were treated for 4 weeks.Before and after treatment,the angina attacks,dosage of nitroglycerin,traditional Chinese medicine syndrome score,quality of life score,blood lipid,coagulation index and clinical total efficacy were observed and recorded.Results:After 4 weeks of treatment,the attack times and duration of angina in the two groups were both decreased compared with those before treatment.And the treatment group was more significantly reduced than the control group,the difference was statistically significant(p<0.05);the consumption of nitroglycerin of the treatment group was 90.0%,which was better than 67.5%of the control group,the difference was statistically significant(p<0.05);the total effective rate of the treatment group was 90%,which was better than 65%of the control group,the difference was statistically significant(p<0.05);the traditional Chinese medicine(TCM)syndrome score of the experimental group was lower than that of the control group,the differences was significant(p<0.05).The improvement of low density lipoprotein(LDL-C),total cholesterol(TC)and prothrombin time(PT)in the experimental group was better than that in the control group(p<0.05).During the study,there were no obvious adverse reactions in both groups.Conclusion:Gualou Xiebai Banxia decoction combined with Danshen decoction can effectively relieve the attack of angina and the consumption of nitroglycerin,improve clinical symptoms,regulate blood lipid and blood flow state,and improve the quality of life of patients with UA,with good clinical efficacy and safety.

Professor Jun Li Treating Vascular Dementia from Mutual Conclusion of Phlegm and Blood Stasis

Professor Jun Li believes that the main etiology and pathogenesis of vascular dementia is the combination of phlegm and blood stasis.The symptoms include feeling faint and declined senses in organs of the head,caused by mystery reason.To cure phlegm and blood stasis simultaneously,the therapy promotes the notion of“resolving phlegm and stimulating the circulation of blood,liberate brain orifices,”and treatments with the addition and removal of“Naotaitong Decoction,”which has an amazing clinical curative effect.This paper examines Professor Jun Li’s theoretical foundations and ideas from the syndrome differentiation and treatment of phlegm and blood stasis,systematically examines the curative effect and mechanism of Naotaitong Decoction in the treatment of vascular dementia,and examines the prescription and medication of typical cases for readers,in the hopes of providing guidance to clinical diagnosis and treatment of this disease.

On the Treatment of Kidney Fibrosis from the Theory of Internal Deficiency of Qi and the Coexistence of Phlegm and Blood Stasis

Traditional Chinese medicine believes that the etiology and pathogenesis of renal fibrosis are characterized by deficiency of the lung,spleen and kidney,and phlegm,blood stasis,dampness and poison.The positive and the evil can influence each other and cause and effect each other,forming the pathological characteristics of the deficiency,the deficiency,the deficiency and the reality.Chinese medicine treatment of the disease has its unique advantages,external and internal injury equal emphasis,correction and dispelling evil and regulation.From the point of view of"deficiency of qi and coexistence of phlegm and blood stasis",the treatment of renal fibrosis can provide theoretical basis for the treatment of the disease.

Effect of Traditional Chinese Medicine combined with Western Medicine on blood lipid levels and inflammatory factors in patients with angina pectoris in coronary heart disease identified as intermingled phlegm and blood stasis syndrome:a network Meta-anal

OBJECTIVE:To evaluate the clinical efficacy of Traditional Chinese Medicine prescriptions for resolving phlegm in the treatment of angina pectoris of phlegmstasis coronary heart disease by a network Meta-analysis.METHODS:Randomized controlled trials(RCTs)on clinical efficacy of CHD angina pectoris with interaction of phlegm and blood stasis were searched in PubMed,Springer,the Cochrane Library and Chinese-language databases China National Knowledge Infrastructure,China Science and Technology Journal Database,and Wanfang Data from their inception to December 2021.Literature was screened and literature bias risk was assessed by RevMan5.4 software.The overall response rate,the duration of angina attack,the levels of serum lipids such as total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C),and expression of hypersensitive C-reactive protein(hs-CRP)were selected as outcome indicators for network Meta-analysis and mapped using Stata15.1 software.RESULTS:Totally,26 RCTs were included,involving 2098 participants.There were 6 TCM formulas with the effects of dispelling phlegm and removing blood stasis.Taking conventional Western Medicine as the common intervention measures,the results showed that the overall response improvement rate from high to low was displayed as modified Xiaoxianxiong decoction(小陷胸汤,MXD),Danlou tablet(丹蒌片,DT),modified Gualou Xiebai Banxia decoction(瓜蒌薤白半夏汤,MGXBD),modified Wendan decoction(温胆汤,MWD),modified Zhishi Xiebai Guizhi decoction(枳实薤白桂枝汤,MZXGD),and modified Erchen decoction(二陈汤,MED).The sequence of angina attack duration improvement from high to low was MZXGD,MGXBD,DT,MWD,MXD.The sequence of TC improvement from high to low was MZXGD,MED,DT,and MGXBD.Sequence of improving TG from high to low was MED,MZXGD,MGXBD,and DT.For LDL-C improvement,the effect from good to poor was MZXGD,MGXBD,DT,and MED.With regard to HDL-C improvement,the effect was ranked as MED,MZXGD,MGXBD,and DT from good to poor.hs-CRP expression from high to low was MZXGD,MXD,MED,MWD,and MGXBD.CONCLUSION:TCM formula with the effects of dispelling phlegm and removing blood stasis combined with conventional Western Medicine has obvious advantages in treating CHD angina pectoris with interaction of phlegm and blood stasis.MZXGD has great potential in increasing the overall response rate,reducing Duration of angina attack improving blood lipids,and reducing inflammatory factors.However,due to the limitations of extant studies,the conclusions of this study need to be confirmed by numerous reasonably-designed RCTs.

Plasma metabolic biomarkers for syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis

OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome. METHODS： The plasma metabolite profiles of 31 patients with the syndrome of phlegm and blood stasis in hyperlipidemia and As, 6 patients with syn- dromes without phlegm and blood stasis, and 10 healthy subjects were analyzed by gas chromatog- raphy-mass spectrometry （GC-MS）. Partial least squares-discriminant analyses （PLS-DA） were used to carry out the pattern-recognition analyses of the data. The plasma metabolic biomarkers of patients were obtained by variable importance plot value （VlP value） and Student＇s t-test. The structures ofbiomarkers were defined by the National Institute of Standards and Technology （NIST） database. RESULTS： PLS-DA score plots of plasma metabo- Iomes did not show overlap between the phlegm-blood stasis syndrome group and syn- dromes without phlegm and blood stasis group, whereas significant differences in the concentra- tions in the plasma of 5 metabolites were found （P〈 0.05）. They were identified as urine, isoleucine, gluc- uronic acid, palmitic acid and glycerol by searching in NIST database. The concentrations of four metab- olites in the plasma of patients with syndrome of phlegm and blood stasis were higher than those with syndromes without phlegm and blood stasis, whereas the glycerol concentration was lower. CONCLUSION： Compared with patients with syn- dromes without phlegm and blood stasis, five me- tabolites showed abnormal levels in patients with the syndrome of phlegm and blood stasis. These metabolites could be diagnostic and prognostic biomarkers.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

The Proteomic Research of the Cure of Experimental Diabetes Deafness by Granules of Eliminating Phlegm and Removing Blood Stasis

Objective: Observing the expression changes of serum proteome in model rats after intervention of the Granules of Eliminating Phlegm and Removing Blood Stasis (豁痰祛瘀颗粒 also known as GEPRB), screening out and identifying the differentially expressed proteins by mass spectrometry and bioinformatics analysis, discussing the molecular mechanism of control the Diabetes deafness by GEPRB. Methods: By use of proteomics technology, the serum protein serum proteome of the control group, model control group, Duxil and each observation group were observed for 2-DE gel pattern matching, and the difference in the relative content of 2 times was chosen for the differentially expressed proteins. Identification of differentially expressed proteins by MALDI-TOF MS/MS, the authors further analysis the phosphorylation, subcellular localization, interaction, direct regulation, and transmembrane of the differences proteins by the way of bioinformatics analysis. Sixty SPF level SD rats elected in diabetic rats model group (abbreviated as DM group) were be randomly divided into 5 groups based on random number sheet, namely model control group, positive drug control group (Du-ke-xi group) and Mai-tong-fang high, medium and low dose group respectively. In addition, set of normal control group. 10 rats in each group. Results: By Coomassie brilliant blue staining, identified 51 differential protein spots dug from 2-D gel by mass spectrometry, successfully identified 13 non-redundant proteins. Most of the identified proteins were secreted protein and belong to different protein families. There were about 12 proteins have the transmembrane region from the authors’ result, ten of them were plasma membrane proteins. Conclusion: It’s suggesting that 13 differential proteins is most likely the protein response to GEPRB in vivo, these proteins may play key role for the treatment of GEPRB to Diabetes deafness. The two highly differentially expressed proteins Apolipoprotein E (apoE) and C3 may be a potential drug target of GEPRB.

Theory discussion on airway remodeling of bronchial asthma

According to modern research,the pathogenesis of asthma mainly includes airway inflammation,airway hyperresponsiveness,airway remodeling,etc.Airway remodeling is the key factor that leads to the progress of asthma,and it is also the main factor that leads to airway hyperresponsiveness and irreversible airflow restriction.Traditional Chinese medicine believes that"phlegm and blood stasis"block the airway and narrow the lumen is the most important factor in the treatment of asthma.

Diagnostic value of traditional Chinese medical dialectical classification in hashimoto's thyroiditis complicated with suspicious nodules

Objective:To explore the diagnostic value of traditional Chinese medical(TCM)dialectical classification in Hashimoto's thyroiditis complicated with suspicious nodules.Methods:The clinical data of patients with Hashimoto's thyroiditis complicated with thyroid nodules in the Department of Breast and thyroid surgery of Weifang Hospital of traditional Chinese Medicine from January 2018 to December 2019 were collected.The patients were examined by 2 or more experienced TCM doctors,and the four diagnostic data were obtained,and then the relevant syndrome types of the patients were judged according to the data.According to the color Doppler ultrasonographic features of thyroid nodules,the patients who met the indication of fine needle aspiration biopsy of thyroid nodules were selected and underwent fine needle aspiration biopsy of thyroid nodules before operation.To analyze the clinical diagnostic value of that the ultrasonic mode used in this study and thyroid cytopathology Bethesda report system combine dialectical classification of traditional Chinese medicine in Hashimoto's thyroiditis complicated with suspected thyroid nodules.Result:A total of 89 patients with Hashimoto's thyroiditis complicated with thyroid nodules were collected.according to the ultrasonic mode,the difference between different modes was statistically significant(P<0.05).The mode of color ultrasound is also related to the dialectical classification of traditional Chinese medicine.The patients with high malignant risk score are mainly qi depression and phlegm stagnation,phlegm and blood stasis,while those with low score are exuberant liver fire and heart liver yin deficiency.According to the study of different The Bethesda System for Reporting Thyroid Cytopathology(TBSRTC)classification,the dialectical classification of patients with higher TBSRTC classification was more inclined to qi depression and phlegm stagnation,phlegm and blood stasis,and there was significant difference between different classification(P<0.05).Conclusion:Qi depression and phlegm obstruction,phlegm and blood stasis have high ultrasound malignant risk score and high TBSRTC classification grade in patients with Hashimoto's thyroiditis complicated with suspected thyroid nodules,which has important clinical diagnostic value.

Intra-set correlation analysis of medical records of thyroid cancer treated by traditional Chinese medicine Master ZHOU Zhongying

Objective Based on intra-set correlation analysis, this paper deconstructs the clinical medical records of traditional Chinese medicine(TCM) Master ZHOU Zhongying in treating thyroid cancer, and analyzes the experience in “mechanism-syndrome-medicine-prescription” for thyroid cancer.Methods Through Medcase data processing platform, based on Frequent Pattern(FP)-Growth enhanced correlation analysis algorithm, the medical records of Professor ZHOU Zhongying for the treatment of thyroid cancer from June 1, 2001 to February 28, 2015 were analyzed within the set.Results This study involved 43 medical records, 43 patients, and 167 visits. After processing intra-set correlations, 28 groups of highly correlated symptoms, 21 groups of highly correlated tongue images, 10 groups of highly correlated pulse conditions, 28 groups of highly correlated pathogenesis, 34 groups of highly correlated herbs, and 26 groups of highly correlated western medicine diagnosis were selected. Professor ZHOU Zhongying treats thyroid cancer according to syndrome differentiation. Symptoms with more association rules included neck swelling, neck pain, cough, and dry mouth;tongue images with more association rules included dark purple tongue, dark red tongue, and fissured tongue;pulse conditions with more association rules were wiry pulse, thready pulse, small pulse, and slippery pulse;the pathogenesis with more association rules was phlegm and blood stasis, damp-heat accumulation,and impairment of both Qi and Yin;herbs with more association rules were Chaihu(Bupleuri Radix), Zeqi(Sun Euphoribiae Herb), and Tiandong(Asparagi Radix);western medicine diagnosis with more association rules included thyroid cancer, insomnia, and chronic gastritis.Conclusion Thyroid cancer mostly presents as deficiency in origin and excess in manifestations. The basic pathogenesis is phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin, which are closely related to liver, kidney, and spleen. Professor ZHOU Zhongying adopts both attack and supplement approaches as the general treatment principle, with a strong emphasis on regulating Qi and relieving depression, eliminating phlegm and resolving stagnation, eliminating dampness and turbidity, clearing fire and destroying poison, moistening dryness and softening hard mass, invigorating Qi and nourishing Yin, and paying attention to nourishing liver and kidney, invigorating spleen and stomach,while protecting the heart and lungs.

Research Progress of Gualou Xiebai in the Treatment of Coronary Heart Disease

Gualou Xiebai is a basic prescription for the treatment of angina pectoris in Synopsis of the Golden Chamber.This article is a summary of the theoretical research and clinical application of Gualou Xiebai,in hope to promote the use of Gualou Xiebai in clinical practice.

Summary of 32 Patients with Cardiac Syndrome X Treated by TCM Therapy of Regulating Qi Relieving Chest Stuffiness and Promoting Blood Circulation

Objective： To evaluate the clinical effect of Liqi Kuanxiong Huoxue method （宽胸活血,LKH, traditional Chinese medicine, TCM therapeutic method for regulating qi, relieving chest stuffiness and promoting blood circulation） in treating patients with cardiac syndrome X （CSX）. Methods： The prospective, non-randomized controlled study was conducted on 51 selected patients with CSX, who were non-randomly assigned to 2 groups, the treated group treated with LKH in addition to the conventional treatment （32 patients）, and the control group treated with conventional treatment （19 patients） like nitrate, diltiazem hydrochloride, etc. The treatment course was 14 days. The changes of such symptoms as angina pectoris, TCM syndrome and indexes of treadmill exercise test before and after treatment were observed. Results： After treatment, such symptoms as chest pain and stuffy feeling and palpitation in the treated group were improved more than those in the control group （P〈0.05）; the total effective rate on angina pectoris and TCM syndrome in the treated group was better than that in the control group （P〈0.05）. The treadmill exercise test showed that the maximal metabolic equivalent （Max MET）, the time of angina onset and ST segment depression by 0.1 mV were obviously improved after treatment in both groups, but the improvement in the treated group was better than that in the control group respectively （P〈0.05）. Conclusion： The LKH method could reduce the frequency of angina attacks and improve the clinical condition of patients with CSX.

Effect of Yinian Jiangya Yin on Primary Hypertension in Early Stage—A Clinical Observations on 40 Patients

Objective: To observe the effect of Yinian Jiangya Yin (Decoction for lowering blood pressure to prolong life) on patients with early hypertension and its mechanism on the function of vascular endotheliocytes. Methods: The 79 patients with early primary hypertension belonging to the TCM syndrome of stagnation of phlegm and blood stasis in meridians and hyperactivity of the liver-yang were randomly divided into a treatment group of 40 patients treated with Yinian Jiangya Yin and a control group of 39 patients treated with Tianma Gouteng Yin (Decoction of Gastrodia and Uncaria). The changes in score of TCM syndrome and in blood pressure before and after treatment were observed in the two groups. The contents of nitrogen monoxide (NO) and endothelin (ET) in serum after treatment were determined. Results: There was a statistical difference (P<0.05) in score of TCM syndrome, effect of lowering blood pressure, and the contents of ET and NO in serum after treatment between the two groups. Conclusion: The effect of Yinian Jiangya Yin on improving TCM syndrome of patients with primary hypertension in early stage and on lowering blood pressure may be related to its regulating the imbalanced condition between ET and NO for restoring the function of endothelium-dependent vasodilation.